---
title: Interpreting PROTAC outputs
description: >-
  Linker libraries, ternary complex coordinates, DC50 predictions, Dmax scores,
  and hook effect assessments.
tags:
  - protac
  - outputs
---

These tools return linker libraries with drug-likeness properties, ternary complex 3D coordinates, and degradation metrics like DC50, Dmax, and hook effect risk — letting you rank degrader candidates and carry the most feasible ones into ADMET, retrosynthesis, and docking validation.

## Interpreting PROTAC outputs

## PROTAC Linker Enumerate output

| Field | Type | Description |
|-------|------|-------------|
| `warhead_smiles` | string | Input warhead SMILES |
| `e3_ligand_smiles` | string | Input E3 ligand SMILES |
| `e3_system` | string | E3 ligase system used |
| `total_linkers` | number | Number of linkers generated |
| `scaffold_distribution` | object | Count of linkers per scaffold type |
| `linkers` | array | Individual linker results |

### Linker fields

| Field | Type | Description |
|-------|------|-------------|
| `linker_smiles` | string | SMILES of the linker fragment |
| `full_protac_smiles` | string | SMILES of the complete PROTAC (warhead-linker-E3 ligand) |
| `linker_length` | number | Atom count in shortest linker path |
| `rotatable_bonds` | number | Number of rotatable bonds in the linker |
| `scaffold_type` | string | Linker scaffold classification |
| `molecular_weight` | number | Total PROTAC molecular weight (Da) |
| `clogp` | number | Calculated partition coefficient |
| `tpsa` | number | Topological polar surface area (A^2) |
| `hbd` | number | Hydrogen bond donors |
| `hba` | number | Hydrogen bond acceptors |
| `qed` | number | Quantitative estimate of drug-likeness (0-1) |
| `sa_score` | number | Synthetic accessibility score (1-10, lower = easier) |
| `diversity_rank` | number | Rank by chemical diversity within the library |

### Scaffold distribution example

```json
{
  "peg": 15,
  "alkyl": 12,
  "piperazine": 10,
  "triazole": 8,
  "hybrid": 5
}
```

### Drug-likeness considerations for PROTACs

PROTACs violate Lipinski's Rule of Five due to their large size. Use PROTAC-specific guidelines:

| Property | Traditional drug | PROTAC acceptable range |
|----------|-----------------|------------------------|
| Molecular weight | < 500 Da | 700-1200 Da |
| cLogP | < 5 | < 10 |
| HBD | < 5 | < 8 |
| HBA | < 10 | < 18 |
| TPSA | < 140 A^2 | < 300 A^2 |
| Rotatable bonds | < 10 | < 20 |

## PROTAC Ternary Model output

| Field | Type | Description |
|-------|------|-------------|
| `protac_smiles` | string | Input PROTAC SMILES |
| `poi_structure` | string | POI structure identifier |
| `e3_structure` | string | E3 ligase structure identifier |
| `e3_system` | string | E3 ligase system |
| `num_conformers` | number | Number of conformers sampled |
| `best_conformer` | object | Top-scoring ternary complex |
| `conformers` | array | All conformer results |
| `complex_pdb_url` | string | Download URL for the best complex PDB file |

### Conformer fields

| Field | Type | Description |
|-------|------|-------------|
| `conformer_id` | number | Conformer index (1-based) |
| `feasibility_score` | number | Overall feasibility score (0-1, higher = better) |
| `buried_surface_area` | number | Buried surface area at POI-E3 interface (A^2) |
| `shape_complementarity` | number | Shape complementarity score (0-1) |
| `clash_count` | number | Number of steric clashes |
| `interface_residues_poi` | number | POI residues at the interface |
| `interface_residues_e3` | number | E3 ligase residues at the interface |
| `linker_strain_energy` | number | Linker conformational strain (kcal/mol) |
| `pdb_url` | string | Download URL for this conformer's PDB file |

### Feasibility score interpretation

| Score Range | Interpretation |
|-------------|----------------|
| 0.8 - 1.0 | Excellent: strong productive interface, minimal clashes |
| 0.6 - 0.8 | Good: reasonable interface, proceed to degradation scoring |
| 0.4 - 0.6 | Marginal: weak interface, consider linker modifications |
| < 0.4 | Poor: unlikely to form productive ternary complex |

### Buried surface area interpretation

| BSA Range (A^2) | Interpretation |
|-----------------|----------------|
| > 2000 | Large, stable interface |
| 1500 - 2000 | Moderate interface, typical for productive PROTACs |
| 1000 - 1500 | Small interface, may require optimization |
| < 1000 | Minimal interface, likely non-productive |

## PROTAC Degradation Score output

| Field | Type | Description |
|-------|------|-------------|
| `protac_smiles` | string | Input PROTAC SMILES |
| `e3_system` | string | E3 ligase system |
| `dc50_nm` | number | Predicted DC50 in nanomolar |
| `dmax_pct` | number | Predicted maximum degradation percentage |
| `hook_effect_risk` | string | Hook effect risk assessment |
| `cooperativity_alpha` | number | Ternary complex cooperativity factor |
| `overall_grade` | string | Summary grade (A-F) |
| `component_scores` | object | Breakdown of scoring components |

### Component scores

| Field | Type | Description |
|-------|------|-------------|
| `linker_score` | number | Linker property contribution (0-1) |
| `ternary_score` | number | Ternary complex geometry contribution (0-1, requires ternary_job_id) |
| `physicochemical_score` | number | Drug-likeness contribution (0-1) |
| `permeability_score` | number | Predicted cell permeability (0-1) |

### DC50 interpretation

| DC50 Range | Grade | Interpretation |
|------------|-------|----------------|
| < 10 nM | A | Highly potent degrader |
| 10 - 100 nM | B | Potent degrader |
| 100 nM - 1 uM | C | Moderate degrader |
| 1 - 10 uM | D | Weak degrader |
| > 10 uM | F | Unlikely to achieve meaningful degradation |

### Dmax interpretation

| Dmax Range | Grade | Interpretation |
|------------|-------|----------------|
| > 90% | A | Near-complete degradation |
| 70 - 90% | B | Good degradation |
| 50 - 70% | C | Partial degradation |
| 30 - 50% | D | Limited degradation |
| < 30% | F | Insufficient degradation |

### Hook effect risk levels

| Risk Level | Description |
|------------|-------------|
| `"low"` | No bell-shaped dose-response expected |
| `"moderate"` | Some binary complex competition at high concentrations |
| `"high"` | Strong binary complex formation, expect reduced efficacy at > 1 uM |

### Cooperativity interpretation

| Alpha Value | Interpretation |
|-------------|----------------|
| > 1.0 | Positive cooperativity (ternary complex is stabilized) |
| 1.0 | No cooperativity (binding events are independent) |
| < 1.0 | Negative cooperativity (ternary complex is destabilized) |

## Read next